Mutant Gene Raises Risk of Parkinson's

Fivefold Higher Parkinson's Risk With Gaucher's Disease Gene

From the WebMD Archives

Oct. 21, 2009 -- A clue from a rare disease has led to the discovery of gene mutations that increase risk of Parkinson's disease fivefold.

People with Gaucher's disease have a defective GBA gene. Doctors studying the rare, inherited illness noticed that these patients are at increased risk of the much more common Parkinson's disease.

It's clear that a mutant GBA gene doesn't doom a person to Parkinson's. If it did, everyone with Gaucher's disease would also have Parkinson's. But could the gene predispose a person to Parkinson's?

NIH researcher Ellen Sidransky, MD, thought so. So she contacted virtually every other Gaucher's disease researcher -- 64 of them at 16 centers around the globe -- to collaborate in a massive study.

"Having mutations in the GBA gene puts you at risk of Parkinson's disease," Sidransky tells WebMD. "And five times more Parkinson's patients have this than controls."

An individual's genetic background also plays a role. GBA mutations are particularly common in Ashkenazi Jews. However, not everyone with a mutant form of GBA gets Parkinson's.

"I am pretty convinced that not every patient with this mutation will go on to get Parkinson's disease," Sidransky says. "So there are clearly other environmental or genetic factors that play into the equation."

What is it about the GBA gene that's linked to Parkinson's? It's known that the gene encodes an enzyme, glucocerebrosidase or GBA. But what role GBA plays in Parkinson's disease isn't yet known.

"The ultimate challenge is to establish the mechanism contributing to this association," Sidransky and colleagues note in their report, which appears in the Oct. 22 issue of The New England Journal of Medicine.

That search represents an entirely new and promising avenue of research.

"It gives us new theories and ideas that have all kinds of clinical and therapeutic implications," Sidransky says. "This is a great example of why it is important to study rare genetic disorders. Because sometimes you end up with findings that have implications not only for the rare disorder but also for a common disease."

WebMD Health News Reviewed by Louise Chang, MD on October 21, 2009



Sidransky, E. The New England Journal of Medicine Journal, Oct. 22, 2009; vol 3614: pp 1651-1661.

Ellen Sidransky, MD, chief, section of molecular neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Md.

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